Previous work from the Neuropharmacology of Cognition project has addressed the close association between attention and motivational state of depressed patients and normals with their cognitive performance. Testing with intravenous naloxone has demonstrated that behavioral changes such as increased depression and anxiety can lead to impaired memory performance. Those observations have led us to expansion in our investigations examining the effects of neuropharmacologic manipulations on the affective and cognitive responses of Alzheimer's patients. This year, we have observed that these patients show marked cognitive and affective sensitivity to the cholinergic antagonist scopolamine and that the behavioral response of Alzheimer patients to naloxone is at a lower dose than previously found with young normals. We are currently examining the effect of age on the response to scopolamine and maloxone with a cohort of aged controls. We are also now in the initial stages of testing the cognitive, behavioral and neuroendocrine reactions of Alsheimer patients and controls to the cholinergic agonists, arecholine and nicotine. In our continued efforts to explore the links between cognition and affective state and its neuropharmacology, we are also actively investigating a therapeutic drug strategy with monoamine oxidase inhibitors in this population of dementia patients.